Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

The Food and Drug Administration on Tuesday disclosed four letters issued to the companies by its marketing enforcement division.

The letter to Lilly cites a print advertisement for the antidepressant Cymbalta, which is approved to treat depression, generalized anxiety disorder, diabetic nerve pain and the pain ailment fibromyalgia. According to the FDA, Lilly's ad does not adequately display information about the drug's side effects, a requirement for all pharmaceutical promotions.

The Indianapolis-based company said it is working to remove the materials from marketing circulation.

"Lilly is committed to providing clinically accurate and balanced promotional materials to health care professionals and patients," the company said in a statement.

The FDA's letter to Cephalon, based in Frazer, Pa., makes similar complaints about missing risk information in the company's promotional cards for Treanda, a lymphoma treatment.

The FDA says the card is "false or misleading because it omits important risk information." The drug has been linked to serious infections, skin reactions and other side effects.

In the letter to Amylin, regulators take issue with statements made by the company while promoting its diabetes drug Byetta at a conference in Washington D.C. last summer. According to the letter, several statements promoted the drug for unapproved uses and "overstate the efficacy of Byetta."

San Diego-based Amylin co-markets Byetta with Lilly.

The companies said in a joint statement that they have already responded to FDA's letter and, "will take action as needed in order to ensure all product communications adhere to regulatory requirements."

Similarly, FDA reviewers said Bayer's script for a presentation on its birth control implant Mirena "overstates the efficacy" and "presents unsubstantiated claims," according to the letter.

A spokeswoman for Bayer Healthcare Pharmaceuticals said the company discontinued the promotional program last February. She confirmed that the German conglomerate, based in Wayne, N.J., received the letter Dec. 30 and will respond by Thursday Jan. 14, as requested by FDA.